Life-threatening opportunistic infection (OI) and Kaposi's sarcoma (KS) have appeared as an epidemic among male homosexuals during the last 2 years. This appears to be associated with an acquired immunodeficiency syndrome (AIDS) characterized by skin test anergy, impaired lymphocyte blastogenesis (LB) and low levels of helper T cells with an inverted helper:suppressor ratio. We have recently studied 33 patients at "high risk" of this syndrome, 28 of whom were ambulatory with performance status 0-1. These patients also showed AIDS as described above. In addition, they showed a suppressor cell for LB but not for antibody synthesis, low monocyte adherence, high serum thymosin alpha1, high serum lysozyme and normal ADCC and natural killer (NK) cell activity. A program has been established for the referral and study of "high risk," OI and KS patients including complete medical, social and immunological evaluation. In this project we will: (1)\fully characterize the immunodeficiency; (2)\investigate its etiology and pathogenesis; (3)\investigate in vitro approaches to immunorestorative therapy; and (4)\develop in vivo immunorestoration therapy and develop an approach to the therapy of KS. The immune parameters to be studied include delayed hypersensitivity, LB, cytomegalovirus immunity, graft-versus-host reactions, suppressor cell activity, T-cell subsets, monocyte function and RES function. Immunorestoratives to be studied include thymic hormones, azimexon, isoprinosine, indomethacin and cimetidine. Therapy for KS will include, in addition to immunorestoration, interferon, VP-16 and combination chemotherapy. Important data will be obtained on the theory of immunosurveillance, on this particular immune deficiency syndrome, on immunorestorative therapy, and on KS and its therapy. In addition, useful prevention and therapy for what appears to be a major health problem in a major population group will be developed. This project is unique because it focuses on patients with the potential to develop AIDS, OI and KS, attempts to define and correct etiological factors and to render therapy before the development of life-threatening OI, KS or other malignancies.